This invention in is the field of non-invasive optical measuring techniques and relates to a method for determining the concentration of a substance in the patient""s blood, such as glucose, hemoglobin, drugs or cholesterol.
Optical methods of determining the chemical composition of blood include spectrophotometric measurements which enable the indication of the presence of various blood constituents based on known spectral behaviors of these constituents. These spectrophotometric measurements may be effected either in vitro or in vivo. The measurements in vitro are invasive, i.e. require a blood sample to be physically withdrawn and investigated. At present, these measurements have become unpopular, due to the increasing danger of infection.
The non-invasive optical measurements in vivo may be briefly divided into two main groups based on different methodological concepts. The first group represents a so-called xe2x80x9cDC measurement techniquexe2x80x9d, and the second group is called xe2x80x9cAC measurement techniquexe2x80x9d.
According to the DC measurement technique, any desired location of a blood perfused tissue is illuminated by the light of a predetermined spectral range, and the tissue reflection and/or transmission effect is studied. Notwithstanding the fact that this technique provides a relatively high signal-to-noise ratio, the results of such measurements depend on all the spectrally active components of the tissue (i.e. skin, blood, muscles, fat, etc.), and therefore they need to be further processed to separate the xe2x80x9cblood signalsxe2x80x9d from the detected signals. Moreover, proportions of the known components vary from person to person and from time to time. To resolve this problem, a calibration must periodically be provided, which constitutes an invasive blood test and therefore renders the DC technique of optical measurements to be actually invasive.
The AC measurement technique focuses on measuring only the xe2x80x9cblood signalxe2x80x9d of a blood perfused tissue illuminated by a predetermined range of wavelengths. To this end, what is actually measured is a time-dependent component only of the total light reflection or light transmission signal obtained from the tissue.
A typical example of the AC measurement technique is a known method of pulse oximetry, wherein a pulsatile component of the optical signal obtained from a blood perfused tissue is utilized for determining the arterial blood oxygen saturation. In other words, the difference in light absorption of the tissue measured during the systole and the diastole is considered to be caused by blood that is pumped into the tissue during the systole phase from arterial vessels and therefore has the same oxygen saturation as in the central arterial vessels. Not only can the oxygen saturation be determined, but in a similar way, concentrations of other chemical elements in the arterial blood can be determined.
The major drawback of such an AC measurement technique is its relatively low signal-to-noise ratio, as compared to that of the DC measurement technique, especially in cases where an individual has a poor cardiac output, insufficient for providing a pulsatile signal suitable for accurate measurements.
Various methods have been suggested to enhance the natural pulsatile signal of an individual for effecting non-invasive optical measurements.
U.S. Pat. No. 4,883,055 discloses a method and device for artificially inducing blood pulse for use with a pulse oximeter. A cuff wrapped around a body member having an artery upstream from a testing site is adapted for applying a squeezing pulse to the body member, the squeezing pulse being synchronized with a normal blood pulse. Oxygen saturation in the arterial blood is determined based on spectrophotometric non-invasive measurements, which are effected according to the general approach of the above-mentioned AC technique.
U.S. Pat. No. 4,927,264 discloses a non-invasive apparatus and a method for measuring blood constituents in venous blood. The venous blood stream is made time-variant by applying pressure with a peak value of the minimum blood pressure to a proximal portion from a measuring part.
U.S. Pat. No. 5,638,816 discloses a blood glucose monitoring system, which provides for inducing an active pulse in the blood volume of a patient according to a predictable cyclic pattern. The induction of an active pulse causes a cyclic change in the flow of arterial blood through a fleshy medium under the test. By actively inducing a change of the blood volume, modulation of the volume of blood can be obtained to provide a greater signal-to-noise ratio. This enables constituents in blood to be detected at concentration levels below those previously detectable in a non-invasive system. Radiation which passes through the fleshy medium is sensed by a detector which generates a signal indicative of the intensity of the detected radiation. Signal processing is performed on the electrical signal to separate those optical characteristics of the electrical signal which are associated with the optical characteristics of the blood.
The techniques disclosed in the above patents use the artificially induced volumetric changes of either arterial or venous blood. Since each of these techniques is specific about the kind of blood under test, they all impose severe restrictions on a value of the artificially applied pressure. This is due to different xe2x80x9cdisturbing pressure valuesxe2x80x9d allowed for different kinds of blood flow. It means that for each kind of blood flow, there is a pressure value that disturbs specifically this kind of flow much more than any other kind. For example, when the artificial pressure at a value of 60 mmHg is applied to a proximal body part, the venous blood flow will be affected, whereas the arterial blood flow will not be affected, since the individual""s diastolic pressure is usually higher than 60 mmHg. The applied artificial pressure definitely should not exceed pressures causing substantial deformation of the tissue, since only blood flow changes are supposed to be detected by optical measurements, and the measurements are to be effected in synchronism with the artificial pulse. However, if such an artificially induced pulse causes uncontrollable changes of the optical properties of the tissue, these changes cannot be distinguished from those caused by the blood flow fluctuations which are the target of the measurements.
There is accordingly a need in the art to facilitate non-invasive, optical measurements of the chemical composition of blood, by providing a novel method combining advantages of both the DC and AC techniques of optical measurements with a high signal-to-noise ratio.
The main idea of the present invention is based on the fact that the light response characteristics (i.e., absorption and/or scattering) of a blood perfused medium dramatically changes when a character of blood flow changes. It has been found by the inventors, that the optical characteristics of a blood perfused fleshy medium (e.g., the patient""s finger) start to change in time, when causing blood flow cessation. In other words, once the blood flow cessation state is established, the optical characteristics start to change dramatically, such that they differ from those of the fleshy medium with a normal blood flow by about 25 to 45%, and sometimes even by 60%.
Hence, the accuracy (i.e., signal-to-noise ratio) of the optical measurements can be substantially improved by taking at least two timely separated measurement sessions each including at least two measurements with different wavelengths of incident radiation. The light response of the medium at these two sessions essentially differ from each other. At least one of the measurement sessions during which the measurement is effected should be chosen either during temporary blood flow cessation, or during the state of transitional blood flow.
In the inventive method, it is therefore suggested to distinguish the normal blood flow from the state of temporary blood cessation by detecting that at least one optical characteristic associated with light absorption and/or scattering of the blood has varied by a predetermined threshold value, and that the character of its change corresponds to the behavior of a time-dependent function. Since variations in the light absorption and/or scattering of blood affect both its light transmitting and light reflecting properties, this at least one detected optical characteristic may constitute either the light transmission or the light reflection of the blood perfused medium.
There is thus provided according to the invention, a non-invasive method of optical measurements for determining the concentration of at least one substance in patient""s blood, the method comprising the steps of:
(a) applying an over-systolic pressure to the patient""s blood perfused fleshy medium with a normal blood flow, so as to cause a state of temporary blood flow cessation for a cessation time period being insufficient for irreversible changes in the fleshy medium;
(b) releasing the over systolic pressure to cause a state of transitional blood flow terminating with the normal blood flow;
(c) selecting at least two timely separated sessions of the optical measurements on the blood perfused fleshy medium such that light response of the medium at said at least two sessions substantially differs from each other, wherein at least one of said at least two sessions is selected within a time period including the state of temporary blood flow cessation and the state of transitional blood flow;
(d) effecting the measurements at said at least two sessions successively, each session including at least two measurements with different wavelengths of incident light; and
(e) determining for each of said at least two sessions a corresponding value of the concentration of said at least on substrate, analyzing the determined values and obtaining a corrected value of said concentration.
It is, of course, possible that both of the at least two sessions of measurements are selected to be between the initially existed and the finally established normal blood flow states, namely during the period of time including the state of temporary blood flow cessation and the state of transitional blood flow. However, one of these at least two sessions may be selected at a state of the normal blood flow.
The blood subjected to the optical test comprises arterial, venous and capillary components. The blood is temporarily xe2x80x9cstagnatedxe2x80x9d in the fleshy medium when the over-systolic pressure is applied, and freely flows through the medium when the pressure is released. Values of the concentrations so obtained should thus be considered more meaningful, as compared to those obtained with the known techniques based on the measurement focused on either the arterial or venous blood component.
By its nature, the method of the present invention is simple and ensures a relatively high signal-to-noise ratio, as compared to the methods utilizing measurements synchronized with the blood pulse. This is owing to the fact that the present invention enables the parameters of the unchanged blood sample to be determined by using two or more readings of significantly distinct amplitudes.
Such an approach has not ever been used or suggested in the prior art. This is actually an advantageous combination of the principles of DC- and AC-techniques. Indeed, on the one hand, owing to high amplitude(s) of the light transmission or reflection signal obtained during the artificially created newly suggested blood flow states, the method resembles the DC-techniques. On the other hand, the method is based on processing the differences between readings of at least two measurements, which is generally similar to the conventional AC-techniques. This method is also advantageous since it is less dependent on motional or other non blood-related artifacts.
As indicated above, the optical characteristics of a blood perfused fleshy medium at the state of blood flow cessation differ from those of the fleshy medium with normal blood flow by about 25 to 45%, and sometimes even by 60%. Conventional methods of pulse oximetry make use of fluctuations of light transmitting characteristics in the range of about 2%. A threshold difference of about 5% between two measurements taken according to the inventive method will fairly satisfy the purpose, namely the concentration determined on the basis of such two measurements will already ensure much more reliable results than those which might be obtained by the pulse oximety technique.
Since the novel method enables to obtain a spectrum of readings differing from each other by up to 60%, more than two sessions may be chosen for effecting the measurements and for further statistical processing of the obtained results. Additionally, it has been found that the method effects an extremely high correlation between values of the concentration obtained from the measurements. Hence, the determining of the concentration may comprise comparison and cross-validation of the results obtained from the two or more measurements. The comparison and cross-validation may include the calculation of the average and a statistical procedure of standard deviation values. Information about a statistical error in a specific measurement may be of a great importance for a physician or a customer.
Values of concentrations obtained by the novel method can also be used for cross-validation of results obtained by the regular AC technique, such as pulse oximetry, i.e., for evaluating reliability of these results.
The method is preferably intended for measuring the concentration of chemical or biological substances which are present in the blood, regardless of the character of its flow. It should, however, be noted that the method can also be used for determining blood oxygen saturation and/or other parameters that depend on the existence of a normal blood pulse, provided additional conditions and approximations are taken into consideration.
The inventive method can be used both for independent measurements and for calibration of other non-invasive methods intended for obtaining similar data and based on measurements synchronized with the blood pulse, for example, methods for the continuous monitoring of blood parameters at departments of intensive care in hospitals.
There is also provided, according to another aspect of the present invention, an optical measurement system for non-invasive determination of concentration of at least one substance in blood, the system comprising:
an illumination-detection arrangement for attaching to a patient""s blood perfused fleshy medium, the illumination-detection arrangement being designed to illuminate the medium with at least two different wavelengths of incident light, detect light response of the illuminated medium and generate data representative thereof;
a pressurizing assembly capable of applying an over-systolic pressure to the blood perfused fleshy medium with the normal blood flow; and
a control unit interconnected between said illumination-detection arrangement and said pressurizing assembly, wherein
said control unit operates the pressurizing assembly so as to selectively apply the over-systolic pressure and cause a state of temporary blood flow cessation for a cessation time period being insufficient for irreversible changes in the fleshy medium, and release the over systolic pressure to cause a state of transitional blood flow terminating with the normal blood flow; and
said control unit operates the illumination-detection arrangement so as to take the optical measurements during at least two different moments such that light absorption of the medium at said at least two moments essentially differs from each other and at least one of said at least two moments is selected within a time period including the state of temporary blood flow cessation and the state of transitional blood flow, the control unit being responsive to said data representative the detect light response of the illuminated medium for analyzing said data and determining the concentration of said at least one substance of the blood.